Research Interests:

Our work is focused on the synthesis of simple living systems from non-living
components, as a means of studying the origin of life. The unifying principle
of biology is Darwinian evolution, so in our view the synthesis of life
is essentially equivalent to the synthesis of a supra-molecular assemblies
that are capable of evolving autonomously. We think that this can be accomplished
by combining two types of replicating system – one encoding genetic
information, and one maintaining spatial localization. A self-replicating
genetic system could in principle be based on molecules such as RNA, DNA,
or any of a number of structurally related molecules which have the ability
to transmit coded information through the replication of complementary
strands.

We are now exploring a variety of chemical strategies for the spontaneous replication
of such nucleic acids. A self-replicating system of spatially localized
compartments could in principle be based on lipid vesicles. We have recently
identified multiple distinct pathways by which fatty acid vesicles can
be made to grow and divide solely under the influence of chemical and
physical forces. Growth occurs when pre-formed vesicles are fed with new
lipid in the form of micelles, or when osmotically swollen vesicles grow
at the expense of relaxed neighboring vesicles. Division can be mediated
by extrusion through small pores in filters, or, in a more prebiotically
realistic scenario, by gentle shear forces acting on thread-like vesicles.
Our efforts on this front are now devoted to understanding the mechanistic
details of these processes. The interactions between the genetic and membrane
components of a protocell pose numerous interesting problems, including
the means by which externally synthesized nucleotides could enter the
protocell. We have recently found that suitably activated nucleotides
can spontaneously cross fatty acid membranes, and can then take part in
template copying reactions in the protocell interior. Nucleic acid molecules
replicating inside replicating vesicles should begin to evolve spontaneously
due to the strong selection for better replication. By pursuing the development
of spontaneously replicating and evolving molecular assemblies in the
laboratory, we hope to uncover constraints on the origin of life on earth,
and perhaps to find explanations for some of the universal aspects of
current biological life.